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Gene Review

SOX4  -  SRY (sex determining region Y)-box 4

Homo sapiens

Synonyms: Transcription factor SOX-4
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Disease relevance of SOX4

  • Differential expression of SOX4 and SOX11 in medulloblastoma [1].
  • Silencing of SOX4 by small interfering RNA transfection induced apoptosis of prostate cancer cells, suggesting that SOX4 could be a therapeutic target for prostate cancer [2].
  • Other genes that were highly ranked for their expression in ACC were those encoding the transcription factors SOX4 and AP-2 gamma, the latter of which also was overexpressed in ACC relative to 175 other carcinomas from 10 anatomical sites that we had previously profiled [3].
  • We now show that human SOX4 is expressed in the normal breast and in breast cancer cells [4].
  • The lung tumor-specific overexpression and demonstration of a comprehensive Ag-specific immune response specific for SOX-4 support the use of this molecule in the development of whole gene-, peptide-, or protein-based vaccination strategies against lung cancer [5].

High impact information on SOX4

  • Syntenin was found to directly associate with the transcription factor Sox4 [6].
  • The establishment of neuronal properties is controlled by Sox4 and Sox11 [7].
  • Interestingly, the capacity of Sox4 and Sox11 to induce the expression of neuronal traits is independent of mechanisms regulating the exit of neural progenitors from the cell cycle [7].
  • TLE-1 and BBC3/PUMA were identified as direct targets of SOX4 [2].
  • Stable transfection of SOX4 into nontransformed prostate cells enabled colony formation in soft agar, suggesting that, in the proper cellular context, SOX4 can be a transforming oncogene [2].

Chemical compound and disease context of SOX4

  • Treatment of T-47D breast cancer cells with the synthetic progestin ORG 2058 directly increased SOX4 transcription, resulting in a 4-fold increase in SOX4 mRNA levels within 4 h of treatment [4].

Biological context of SOX4


Anatomical context of SOX4


Associations of SOX4 with chemical compounds

  • Here we describe that the central domain containing glycine-rich region in Sox4, named CD, is a pivotal pro-apoptotic domain to induce apoptotic cell death [10].
  • Clones with PRA:PRB ratios greater than 15 were associated with diminished progestin responses on both SOX4 and FAS mRNA expression [12].
  • In these cells SOX4 is a progesterone-regulated gene, the expression of which is increased by progestins, leading to a marked increase in SOX-mediated transcriptional activity [4].

Physical interactions of SOX4

  • Ubc9 interacts with SOX4 and represses its transcriptional activity [13].

Co-localisations of SOX4


Regulatory relationships of SOX4

  • Luciferase assays found that Ubc9 specifically repressed SOX4 transcriptional activity in 293T cells [13].
  • It shows that Ubc9 interacts with SOX4 and represses its transcriptional activity independent of its SUMO-1-conjugating activity [13].

Other interactions of SOX4

  • We have studied the expression of Sox4, and the closely related Sox11 gene, in medulloblastomas [1].
  • There is no evidence for clustering of other members of the SOX1, -2, and -3 or SOX4 gene families around the SOX4 locus [9].
  • Assignment of Sox4 to mouse chromosome 13 bands A3-A5 by fluorescence in situ hybridization; refinement of the human SOX4 location to 6p22.3 and of SOX20 to chromosome 17p12.3 [14].
  • The SOX-4 gene is a member of a gene family (SOX and SRY) comprising transcription factors that bind to DNA through their high mobility group (HMG)-type binding domain, and previous reports have implicated Sox proteins in various developmental processes [15].
  • Deletion mapping demonstrated that HMG-box domain of SOX4 is required to mediate the interaction with Ubc9 in yeast [13].

Analytical, diagnostic and therapeutic context of SOX4


  1. Differential expression of SOX4 and SOX11 in medulloblastoma. Lee, C.J., Appleby, V.J., Orme, A.T., Chan, W.I., Scotting, P.J. J. Neurooncol. (2002) [Pubmed]
  2. Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells. Liu, P., Ramachandran, S., Ali Seyed, M., Scharer, C.D., Laycock, N., Dalton, W.B., Williams, H., Karanam, S., Datta, M.W., Jaye, D.L., Moreno, C.S. Cancer Res. (2006) [Pubmed]
  3. Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma. Frierson, H.F., El-Naggar, A.K., Welsh, J.B., Sapinoso, L.M., Su, A.I., Cheng, J., Saku, T., Moskaluk, C.A., Hampton, G.M. Am. J. Pathol. (2002) [Pubmed]
  4. Regulation of the expression and activity by progestins of a member of the SOX gene family of transcriptional modulators. Graham, J.D., Hunt, S.M., Tran, N., Clarke, C.L. J. Mol. Endocrinol. (1999) [Pubmed]
  5. Molecular and immunological evaluation of the transcription factor SOX-4 as a lung tumor vaccine antigen. Friedman, R.S., Bangur, C.S., Zasloff, E.J., Fan, L., Wang, T., Watanabe, Y., Kalos, M. J. Immunol. (2004) [Pubmed]
  6. Cytokine-specific transcriptional regulation through an IL-5Ralpha interacting protein. Geijsen, N., Uings, I.J., Pals, C., Armstrong, J., McKinnon, M., Raaijmakers, J.A., Lammers, J.W., Koenderman, L., Coffer, P.J. Science (2001) [Pubmed]
  7. The establishment of neuronal properties is controlled by Sox4 and Sox11. Bergsland, M., Werme, M., Malewicz, M., Perlmann, T., Muhr, J. Genes Dev. (2006) [Pubmed]
  8. The high mobility group transcription factor, SOX4, transactivates the human CD2 enhancer. Wotton, D., Lake, R.A., Farr, C.J., Owen, M.J. J. Biol. Chem. (1995) [Pubmed]
  9. Characterization and mapping of the human SOX4 gene. Farr, C.J., Easty, D.J., Ragoussis, J., Collignon, J., Lovell-Badge, R., Goodfellow, P.N. Mamm. Genome (1993) [Pubmed]
  10. Functional identification of the pro-apoptotic effector domain in human Sox4. Hur, E.H., Hur, W., Choi, J.Y., Kim, I.K., Kim, H.Y., Yoon, S.K., Rhim, H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  11. SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization. Aaboe, M., Birkenkamp-Demtroder, K., Wiuf, C., Sørensen, F.B., Thykjaer, T., Sauter, G., Jensen, K.M., Dyrskjøt, L., Ørntoft, T. Cancer Res. (2006) [Pubmed]
  12. Effect of overexpression of progesterone receptor A on endogenous progestin-sensitive endpoints in breast cancer cells. McGowan, E.M., Clarke, C.L. Mol. Endocrinol. (1999) [Pubmed]
  13. Ubc9 interacts with SOX4 and represses its transcriptional activity. Pan, X., Li, H., Zhang, P., Jin, B., Man, J., Tian, L., Su, G., Zhao, J., Li, W., Liu, H., Gong, W., Zhou, T., Zhang, X. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  14. Assignment of Sox4 to mouse chromosome 13 bands A3-A5 by fluorescence in situ hybridization; refinement of the human SOX4 location to 6p22.3 and of SOX20 to chromosome 17p12.3. Critcher, R., Stitson, R.N., Wade-Martins, R., Easty, D.J., Farr, C.J. Cytogenet. Cell Genet. (1998) [Pubmed]
  15. Sox-4 messenger RNA is expressed in the embryonic growth plate and regulated via the parathyroid hormone/parathyroid hormone-related protein receptor in osteoblast-like cells. Reppe, S., Rian, E., Jemtland, R., Olstad, O.K., Gautvik, V.T., Gautvik, K.M. J. Bone Miner. Res. (2000) [Pubmed]
  16. Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells. Pramoonjago, P., Baras, A.S., Moskaluk, C.A. Oncogene (2006) [Pubmed]
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